CN101574331A - Lappaconitine transdermal patch and preparation method thereof - Google Patents
Lappaconitine transdermal patch and preparation method thereof Download PDFInfo
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- CN101574331A CN101574331A CNA2009101189289A CN200910118928A CN101574331A CN 101574331 A CN101574331 A CN 101574331A CN A2009101189289 A CNA2009101189289 A CN A2009101189289A CN 200910118928 A CN200910118928 A CN 200910118928A CN 101574331 A CN101574331 A CN 101574331A
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Abstract
The invention discloses a lappaconitine transdermal patch and preparation method thereof. The patch comprises a back sheet, a drug storing layer and a protection layer, wherein, the drug storing layer is composed of the raw materials of lappaconitine and pressure sensitive adhesive, or a right amount of transdermal accelerant is added to finally prepare lappaconitine transdermal patch. The lappaconitine transdermal patch of the invention has the advantages of convenient use, high bioavailability and lasting action, avoids first-pass effect of liver as well as damage to gastrointestinal tract, reduces drug toxicity and side effect, improves bioavailability of drug and safety of treatment, and has obvious effect on anti-inflammatory and analgesia.
Description
Technical field
The present invention relates to a kind of percutaneous plaster and preparation method thereof, particularly a kind of Lappaconitine transdermal patch and preparation method thereof.
Background technology
Pain is modal multiple common symptoms in the medical research clinical disease, and this difficult problem is a great challenge to research worker and doctor.The medicine of nowadays treating pain is based on Western medicine, mainly be divided into non_steroidal anti_inflammatory drug and narcosis analgesic two classes, in this two classes medicine, though anaesthetic analgesic effect is strong, but the side effect of self is big, addiction is arranged, though and the non-steroidal anti-inflammatory analgesic does not have the so big side effect of narcotic analgesic medicine, the untoward reaction of reverse side such as many gastrointestinal tract is also arranged.Medical domain is also constantly being sought the good and anti-inflammation analgesia medicine of side effect minimum of analgesic effect.
Lappaconitine molecular formula lappaconitine hydrobromide molecular formula
Lappaconitine is alkaloid---the Lappaconitine that extracts from Ranunculaceae aconitum plant Aconitum sinomontanum Nakai (Aconitum sinomoutanumNakai), at present the hydrobromate that is mainly lappaconitine that uses clinically.The lappaconitine hydrobromide molecular weight is 683.64, fusing point is 217～221 ℃, be dissolved in methanol, be slightly soluble in water and ethanol, be insoluble in organic solvents such as chloroform, its preparation type is mainly oral formulations and injection, the oral formulations bioavailability is lower, half-life is shorter, needs long-time oral administration, and has the medicine first pass effect; Injection administration inconvenience, pain during injection, prescription is relatively stricter, and improper use is easily caused danger; Lappaconitine hydrobromide ester dissolubility is low, is unfavorable for making paster; Lappaconitine is compared with lappaconitine hydrobromide and has been omitted salify technology, can reduce cost from producing.
Summary of the invention
The objective of the invention is to disclose a kind of Lappaconitine transdermal patch; Another object of the present invention is to disclose the preparation method of this paster.
The objective of the invention is to be achieved through the following technical solutions:
Percutaneous plaster of the present invention comprises backing layer, drug storehouse layer and protective layer, and wherein the raw material of drug storehouse layer consists of:
Lappaconitine: 0.1-2 weight portion
Percutaneous absorption enhancer: 0.1-2 weight portion
Pressure sensitive adhesive: 5-15 weight portion.
Percutaneous plaster of the present invention comprises backing layer, drug storehouse layer and protective layer, and wherein the raw material of drug storehouse layer composition is preferably:
Lappaconitine: 0.5 weight portion
Percutaneous absorption enhancer: 1 weight portion
Pressure sensitive adhesive: 10 weight portions.
Percutaneous plaster of the present invention comprises backing layer, drug storehouse layer and protective layer, and wherein the raw material of drug storehouse layer composition is preferably:
Or lappaconitine: 1 weight portion
Percutaneous absorption enhancer: 0.5 weight portion
Pressure sensitive adhesive: 12 weight portions.
Percutaneous plaster of the present invention comprises backing layer, drug storehouse layer and protective layer, and wherein the raw material of drug storehouse layer composition is preferably:
Or lappaconitine: 1.5 weight portions
Percutaneous absorption enhancer: 1.5 weight portions
Pressure sensitive adhesive: 8 weight portions.
Also can add cosolvent and/or plasticizer in the drug storehouse layer raw material of the invention described above percutaneous plaster, wherein the amount of cosolvent or plasticizer be the amount of amount, Percutaneous absorption enhancer of lappaconitine and pressure sensitive adhesive amount total amount 1-5 doubly.
Also can add cosolvent and/or plasticizer in the drug storehouse layer raw material of the invention described above percutaneous plaster, wherein the amount of cosolvent or plasticizer all is preferably 3 times of total amount of the amount of the amount of amount, Percutaneous absorption enhancer of lappaconitine and pressure sensitive adhesive.
The preparation method of percutaneous plaster of the present invention:
Get the raw material mixing and stirring of above-mentioned drug storehouse layer; Adopt curtain coating technology that said mixture is coated on the backing layer to solvent and volatilize, protective layer on the cooling bonnet, Lappaconitine transdermal patch; Or said mixture is coated on the backing layer, protective layer on the cooling bonnet, Lappaconitine transdermal patch.
Paster of the present invention comprises backing layer, drug storehouse layer and protective layer, it is characterized in that wherein Percutaneous absorption enhancer is meant Laurel nitrogen
In ketone, Mentholum, Borneolum Syntheticum, eucalyptus oil, Fructus Zanthoxyli oil, Oleum Bulbus Allii and Rhizoma Chuanxiong extract, Semen Myristicae extract, propylene glycol, methyl salicylate or the oleic acid one or more.
Paster of the present invention comprises backing layer, drug storehouse layer and protective layer, it is characterized in that wherein pressure sensitive adhesive is meant acrylate pressure sensitive adhesive, Polyisobutylene PSA, polysiloxanes pressure sensitive adhesive or thermo-elasto-plasticity rubber.
Paster of the present invention, Laurel nitrogen
Ketone is by one or more replacements in Mentholum, Borneolum Syntheticum, eucalyptus oil, Fructus Zanthoxyli oil, Oleum Bulbus Allii and Rhizoma Chuanxiong extract, Semen Myristicae extract, propylene glycol, methyl salicylate or the oleic acid; Acrylate pressure sensitive adhesive is replaced by Polyisobutylene PSA, polysiloxanes pressure sensitive adhesive or thermo-elasto-plasticity rubber.
Paster of the present invention, cosolvent is smooth by the fatty acid Pyrusussuriensis, in the polyoxyethylene aliphatic alcohol ether, Polysorbate, fatty glyceride, polyoxyethylene fatty acid ester one or more are united use.
Paster of the present invention, plasticizer is united use by in Kaolin, zinc oxide, titanium dioxide, kieselguhr, glycerol, the propylene glycol one or more.
Wherein, the backing layer of paster of the present invention is that polyurethane film, vinylacetate film, polychloroethylene film are made according to common process; The protective layer of paster is the polyethylene film that common process is made.
The invention provides a kind of easy to use, bioavailability is high, effect persistent " Gaowujiasu " picking and preparation method thereof.Experiment and clinical research show that lappaconitine has antiinflammatory, analgesic effect." Gaowujiasu " picking of the present invention is that glue mixes the type transdermal patch, compares with film controlling type percutaneous plaster in the prior art, and structure is simpler, and cost is lower, and the production cycle is shorter, is easier to produce; In addition, contain controlled release layer in the prior art film controlling type percutaneous plaster, Lappaconitine transdermal patch of the present invention has been removed controlled release layer, the Transdermal absorption result of the test shows: drug transdermal assimilation effect of the present invention is better than prior art film controlling type percutaneous plaster, illustrated that simultaneously lappaconitine makes the paster agent, because the lappaconitine molecular weight is relatively large, release-controlled film is relatively poor to the controlled-release effect of paster, and this curative effect to paster can produce certain influence.Lappaconitine transdermal patch of the present invention is by with lappaconitine and adjuvant rational proportion, guaranteed that not only paster has significant analgesic activity, and reduced the toxic and side effects of medicine, blood drug level is stable, lasting, avoided " first pass effect " and the gastrointestinal of liver to destroy, improved the safety of bioavailability of medicament and treatment, avoid occurring the film controlling type percutaneous plaster and the danger that reasons such as release-controlled film breaks cause occurs, and medication is convenient, no pain, and is remarkable at antiinflammatory, ease pain effect.
Description of drawings
Fig. 1: the different transdermal enhancer Transdermal absorption of " Gaowujiasu " picking curve.
Fig. 2: dissimilar paster Transdermal absorption effect comparison diagrams.
Following experimental example and embodiment are used for further specifying but are not limited to the present invention.
Experimental example 1
The " Gaowujiasu " picking anti-inflammatory of the embodiment of the invention 1 preparation, the pharmacodynamics test of analgesic activity
One, antiinflammatory action test
(1) paraxylene causes the effect of mice auricle swelling (mouse ear swelling test)
1, material
1.1 reagent and apparatus
Dimethylbenzene (analyze pure, Xi'an chemical reagent factory, lot number: 070922); Electron portable balance (model: YB1201, Haikang, Shanghai Electronic Instruments Plant, precision 0.01g); Card punch (specification: 6mm); Tweezers; Syringe (specification: 1ml); The gavage syringe needle; Psychrometer; Picric acid; Microsyringe (Shanghai Medicine Laser Instrument Plant, 50 μ L).
1.2 medicine
" Gaowujiasu " picking; The negative control product are not for containing the paster (self-control) of medicine; Lappaconitine parenteral solution (Gansu Xin Lan pharmaceutcal corporation, Ltd, authentication code: the accurate word H62020888 of traditional Chinese medicines, lot number: 20080201).
1.3 animal used as test
The healthy adult Kunming mouse, male and female half and half, (Lanzhou Institute of Biological Products's Experimental Animal Center provides body weight (20 ± 2) g, the quality certification number: the moving word 14-001 of doctor).
2, grouping and method
Get body weight (20 ± 2) g Kunming mouse, male, be divided at random 5 groups, every group 10, be made as respectively Lappaconitine parenteral solution (0.8mg/kg) control group (I), model control group (paster that does not contain medicine) (II), " Gaowujiasu " picking low dose group (1mg/ subsides) (III), in the " Gaowujiasu " picking dosage group (2mg/ subsides) (IV), " Gaowujiasu " picking high dose group (4mg/ subsides) (V). I group injection Lappaconitine parenteral solution 0.8mg/kg, II～V organizes every group of mouse and pastes corresponding tested material, successive administration 3 days, every day 1 time. The last administration is thrown off tested material after half an hour, with the auris dextra wiped clean, gets dimethylbenzene 0.02mL/ only in mouse right ear before and after two sided coatings with microsyringe with warm water, and every each 0.01mL brings out mouse ear and swells, and left ear is not done any processing. Put to death animal after causing scorching 1h, cut ears along the auricle baseline, lay round auricle, scales/electronic balance weighing with 6mm diameter card punch at same position. Take left and right sides auricle weight difference as swelling, obtain swelling inhibiting rate (%), the antiinflammatory action of comparative drug. Each is organized under mouse the same terms and feeds, freely ingests, and drinking-water, room temperature is controlled at (20 ± 1) ℃, humidity about 60%.
Swelling inhibiting rate (%)=(control group swelling-be subjected to reagent group swelling)/control group swelling * 100%.
3, statistical analysis
(x ± s) expression adopts the SPSS11.5 statistical software to carry out data and processes all data with mean ± standard deviation. Carry out one-way analysis of variance, check with LSD when variance has homogeneous, heterogeneity of variance Dunnett ' s T3 check is carried out comparing between each group. P＜0.05 or P＜0.01 expression difference has conspicuousness.
4, result
Mouse auricle edema method does not need special equipment, and method is easy, instant effect, and dosage is few, and is copied into the power height. Be applicable to the conventional screening of anti-inflammatory agent. This experimental result shows, " Gaowujiasu " picking can significantly suppress the mice caused by dimethylbenzene xylene ear swelling, inhibiting rate is respectively: " Gaowujiasu " picking low dose group (1mg/ subsides) (III) is 13.07%, dosage group (2mg/ subsides) (IV) is 17.03% in the " Gaowujiasu " picking, " Gaowujiasu " picking high dose group (4mg/ subsides) is 36.93% (suitable with the inhibiting rate of Lappaconitine parenteral solution group, the inhibiting rate of Lappaconitine parenteral solution group is 37.77%) (V). Dosage group in the " Gaowujiasu " picking (2mg/ subsides) (IV) (V) compares with model control group with " Gaowujiasu " picking high dose group (4mg/ subsides), difference has conspicuousness (P＜0.05 or P＜0.01), " Gaowujiasu " picking low dose group (1mg/ subsides) (III) compares with model control group, no significant difference (P＞0.05), as shown in table 1, the middle and high dosage of prompting " Gaowujiasu " picking has antiinflammatory action, and antiphlogistic effects has dose dependent.
Table 1 " Gaowujiasu " picking paraxylene causes the impact (x ± s) of mice ear
Annotate: compare with model control group,*P＜0.05，
**P＜0.01
(2) histamine is caused the impact that the mouse capillary permeability increases
1, test material
1.1 medicine and reagent
" Gaowujiasu " picking; The negative control product are not for containing the paster (self-control) of medicine; Lappaconitine parenteral solution (Gansu Xin Lan pharmaceutcal corporation, Ltd, authentication code: the accurate word H62020888 of traditional Chinese medicines, lot number: 20080201); Histamine phosphate (Histamine diphosphate), Shanghai Biochemical Research institute of Chinese Academy of Sciences product; Evans blue, Switzerland's import packing, the Solution on Chemical Reagents in Shanghai purchasing and supply station provides.
1.2 instrument
72-1 type spectrophotometer (Shanghai the 3rd analytical instrument factory product); LD5-2 type centrifuge (Beijing Medical Centrifugal Machine Factory's product); Electron portable balance (model: YB1201, Haikang, Shanghai Electronic Instruments Plant, precision 0.01g); Grainer; Card punch (specification: 2cm).
1.3 animal used as test
The healthy adult Kunming mouse, (Lanzhou Institute of Biological Products's Experimental Animal Center provides body weight (20 ± 2) g, the quality certification number: the moving word 14-001 of doctor).
2, method
Get 50 of mices, male and female half and half, be divided into 5 groups at random, every group 10, be made as respectively lappaconitine hydrobromide injection (0.8mg/kg) matched group (I), model control group (paster that does not contain medicine) (II), " Gaowujiasu " picking low dose group (1mg/ subsides) (III), in the " Gaowujiasu " picking dosage group (2mg/ subsides) (IV), " Gaowujiasu " picking high dose group (4mg/ subsides) (V).I group injection lappaconitine hydrobromide injection 0.8mg/kg sloughs the about 3cm of mouse back with depilator before other treated animal test
2Hair, II～V organizes the right hind of every group of mice by 1cm
2/ only paste and tried thing accordingly, successive administration 6 days, every day 2 times.30min after the last administration throws off and is tried thing, will paste medicine position wiped clean with warm water, at mouse back center subcutaneous injection 0.1% histamine phosphate 0.1mL, tail vein injection 1%Evans indigo plant 5mlkg immediately
-1Behind the 20min, the sacrificed by exsanguination mice peels off skin of back, lays the skin speckle of the position, deep of dyeing with the card punch of diameter 2cm, shred then, soak at twice with 7: 3 acetone and normal saline mixed solution 4mL, each 2h merges immersion, add above-mentioned mixed liquor to 5mL, insulation is hatched 36h until the blue complete obiteration of skin in 60 ℃ of calorstats.Then with 2000rmin
-1Centrifugal 5min gets supernatant, with 72-1 type spectrophotometer colorimetric under the 610nm wavelength, measures the filtrate absorbance.Measured absorbance is carried out statistical procedures.
3, statistical analysis
(x ± s) expression adopts the SPSS11.5 statistical software to carry out date processing to all data with mean ± standard deviation.Carry out one factor analysis of variance, check with LSD when variance has homogeneous, heterogeneity of variance Dunnett ' s T3 check is carried out comparing between each group.P＜0.05 or P＜0.01 expression difference has significance.
4, result
During acute inflammation,, blood vessel-the organize change of barrier function, plasma protein accelerate along with penetrating extravascular tissue speed.This law causes on the scorching basis at the applied chemistry medium, and the dyestuff of quiet notes doses is simultaneously measured the dyestuff of local inflammation intralesional, the variation that can quantitatively and accurately record vascular permeability subsequently.
This result of the test shows that the mice capillary permeability increase that " Gaowujiasu " picking causes histamine has obvious suppression effect (P＜0.05 or P＜0.01), sees Table 2, has antiinflammatory action preferably.
Table 2 " Gaowujiasu " picking causes the influence that the mice capillary permeability increases (x ± s) to histamine
Compare with the model control group group,
*P＜0.05,
*P＜0.01
Two, analgesic activity test
The effect of whipping (tail-flick test) due to radiant heat (radiant heat) stimulated
1, test material
1.1 medicine
" Gaowujiasu " picking; The negative control product are not for containing the paster (self-control) of medicine; Lappaconitine hydrobromide injection (Gansu Xin Lan pharmaceutcal corporation, Ltd, authentication code: the accurate word H62020888 of traditional Chinese medicines, lot number: 20080201).
1.2 instrument
SW-200 photo-thermal tail pain tester; The portable balance of electronics (model: YB1201, Haikang, Shanghai Electronic Instruments Plant, precision 0.01g).
1.3 laboratory animal
The healthy adult Kunming mouse, (Lanzhou Institute of Biological Products's Experimental Animal Center provides body weight (20 ± 2) g, the quality certification number: the moving word 14-001 of doctor).
2, method
Mice is divided into 5 groups at random, every group 12, be made as respectively: lappaconitine hydrobromide injection (0.8mg/kg) matched group (I), blank group (paster that does not contain medicine) (II), " Gaowujiasu " picking low dose group (1mg/ subsides) (III), in the " Gaowujiasu " picking dosage group (2mg/ subsides) (IV), " Gaowujiasu " picking high dose group (4mg/ subsides) (V).During test, animal is put in the Mus tube, tail falls in outside the tube down naturally, uses manual time-keeping, to start (tail flick latency incubation period that photo-thermal to the time that the Mus tail is swung rapidly is the whipping reaction, TFL) as the threshold of pain, regulating load voltage makes basic threshold of pain TFL (pain threshold before the administration) comparatively sensitive for the stimulus intensity of 2-4s to about the 20V, and survey earlier is 3 times during on-test, each 5min at interval, getting its average is the basic threshold of pain.For preventing skin scald, illumination deadline, 10s exceeded.I group injection lappaconitine hydrobromide injection 0.8mg/kg, II～V organizes every group of mice by 1cm
2/ only paste and tried thing accordingly, successive administration 4 days, every day 1 time.30min surveys its threshold of pain after the last administration.Calculate threshold of pain raising rate %.
Threshold of pain raising rate %=(TFL-basis TFL after the administration)/basic TFL * 100%
3, statistical analysis
(x ± s) expression adopts the SPSS11.5 statistical software to carry out date processing to all data with mean ± standard deviation.Carry out one factor analysis of variance, check with LSD when variance has homogeneous, heterogeneity of variance Dunnett ' s T3 check is carried out comparing between each group.P＜0.05 or P＜0.01 expression difference has significance.This group self cross-reference adopts Paired-Samples T Test check.
4, result
The result shows: dosage group in the " Gaowujiasu " picking (2mg/ subsides) (IV) (V) can obviously improve the threshold of pain that radiant heat shines mice with " Gaowujiasu " picking high dose group (4mg/ subsides), with before the administration of this group and the blank group relatively all difference significance (P＜0.05 or P＜0.01) is arranged, see Table 3.
Table 3 " Gaowujiasu " picking stimulates the influence cause pain (x ± s) to the mice radiant heat
Compare with the blank group,
*P＜0.05,
*P＜0.01
It is relatively preceding with the treatment of this group,
#P＜0.05,
##P＜0.01
The screening experiment of experimental example 2 various adjuvants
1, the selection of adhesive test:
Take by weighing lappaconitine, through method adding transdermal enhancer and the different adhesive of embodiment 1, mixing, coating, drying cuts, and measures and holds viscous force (the results are shown in Table 4).
The various adhesive of table 4 hold the viscous force correction data
Experimental result shows that acrylate pressure sensitive adhesive, Polyisobutylene PSA, these three kinds of raw materials of polysiloxanes pressure sensitive adhesive all can be used as the adhesive in the paster preparation process of the present invention, and with the increase of its consumption, and it is bigger to hold viscous force intensity.
2, the selection of transdermal enhancer test:
Take by weighing lappaconitine, method through embodiment 1 adds adhesive, adds the transdermal enhancer of various dose and kind again, adds acrylate pressure sensitive adhesive 80%, mixing, coating, drying cuts, measure drug transdermal absorbing state (the results are shown in accompanying drawing 1), experimental result shows that these three kinds of raw materials of azone, Camphora and oleic acid all can be used as the transdermal enhancer in the paster preparation process of the present invention, and its skin transit dose all can reach requirement.
The comparative experiments of experimental example 3 different percutaneous plaster types
Membrane controlled release type percutaneous drug administration preparation " Gaowujiasu " picking includes protective layer, pressure-sensitive adhesive layer, controlled release layer, drug storehouse storage glue-line and backing layer in the prior art, totally five layers." Gaowujiasu " picking of the present invention is compared with it, and the present invention is simple in structure, and easily with production, the two has essential distinction, and is specific as follows:
| The present invention | Prior art | |
| Patch type | Glue mixes type | Film controlling type |
| Structure | Totally three layers of backing layer, pressure-sensitive adhesive layer, protective layers, simple in structure | Totally five layers of protective layer, pressure-sensitive adhesive layer, controlled release layer, drug storehouse storage glue-line and backing layer, complex structure |
| Curative effect | Significantly | More remarkable |
| Production equipment | Easily produce, production equipment is simple | Be difficult for producing the production equipment complexity |
| Production cycle | Once coating is with short production cycle | Need repeatedly coating, the production cycle is long |
| Safety | Safe | Safety is low, release-controlled film easily break (as the Durogesic incident) |
The test of experimental example 4 Transdermal absorption
Lappaconitine transdermal patch of the present invention and prior art film controlling type percutaneous plaster (No. 92100233.5 patents) have been carried out the Transdermal absorption test, the result shows: the Transdermal absorption effect of Lappaconitine transdermal patch of the present invention obviously is better than prior art (seeing accompanying drawing 2), also illustrated when lappaconitine is made the film controlling type percutaneous plaster simultaneously, because molecular weight is relatively large, release-controlled film is relatively poor to the controlled-release effect of paster, and this also is a Lappaconitine transdermal patch Transdermal absorption obvious results reason of the present invention.
Following embodiment all can realize the beneficial effect of experimental example of the present invention.
The specific embodiment
Embodiment 1: " Gaowujiasu " picking
Lappaconitine: 0.5kg Laurel nitrogen
Ketone: 1kg
Acrylate pressure sensitive adhesive: 10kg;
Get lappaconitine 0.5kg, add acrylate pressure sensitive adhesive 10kg and Laurel nitrogen
Ketone 1kg, the dissolving mixing is prepared into solution; Adopt curtain coating technology, above-mentioned solution coat on backing layer, is volatilized to solvent, protective layer on the cooling bonnet must " Gaowujiasu " picking.
Embodiment 2: " Gaowujiasu " picking
Lappaconitine: 1kg Mentholum: 0.5kg
Polyisobutylene PSA: 12kg;
Get lappaconitine 1kg, add Polyisobutylene PSA 12kg and Mentholum 0.5kg, the dissolving mixing is prepared into solution; Adopt curtain coating technology, above-mentioned solution coat on backing layer, is volatilized to solvent, protective layer on the cooling bonnet must " Gaowujiasu " picking.
Embodiment 3: " Gaowujiasu " picking
Lappaconitine: 1.5kg Percutaneous absorption enhancer: 1.5kg
Polysiloxanes pressure sensitive adhesive: 8kg;
Get lappaconitine 1.5kg, add polysiloxanes pressure sensitive adhesive 8kg and propylene glycol 1.5kg, the dissolving mixing is prepared into solution; Adopt curtain coating technology, above-mentioned solution coat on backing layer, is volatilized to solvent, protective layer on the cooling bonnet must " Gaowujiasu " picking.
Embodiment 4: " Gaowujiasu " picking
Lappaconitine: 1kg acrylate pressure sensitive adhesive 10kg
Polyoxyethylene fatty acid ester: 44kg;
Get lappaconitine 1kg, add acrylate pressure sensitive adhesive 10kg and polyoxyethylene fatty acid ester 44kg, the dissolving mixing is prepared into solution; Adopt curtain coating technology, above-mentioned solution coat on backing layer, is volatilized to solvent, protective layer on the cooling bonnet must " Gaowujiasu " picking.
Embodiment 5: " Gaowujiasu " picking
Lappaconitine: 0.4kg Polysorbate: 0.2kg
Polysiloxanes pressure sensitive adhesive: 10kg propylene glycol: 20kg;
Get lappaconitine 0.4kg, add polysiloxanes pressure sensitive adhesive 10kg, Polysorbate 0.2kg and propylene glycol 20kg, the dissolving mixing is prepared into solution; Adopt curtain coating technology, above-mentioned solution coat on backing layer, is volatilized to solvent, protective layer on the cooling bonnet must " Gaowujiasu " picking.
Embodiment 6: " Gaowujiasu " picking
Lappaconitine: 0.8kg Laurel nitrogen
Ketone: 0.2kg
Acrylate pressure sensitive adhesive: 2kg kieselguhr: 9kg
Glycerol: 3kg;
Get lappaconitine 0.8kg, add acrylate pressure sensitive adhesive 2kg, Laurel nitrogen
Ketone 0.2kg, kieselguhr 9kg and glycerol 3kg, the dissolving mixing is prepared into solution; Adopt curtain coating technology above-mentioned solution coat on backing layer, volatilize to solvent, protective layer on the cooling bonnet must " Gaowujiasu " picking.
Embodiment 7: " Gaowujiasu " picking
Lappaconitine: 1.2kg Laurel nitrogen
Ketone: 0.4kg
Acrylate pressure sensitive adhesive: 10kg;
Get lappaconitine 1.2kg, add acrylate pressure sensitive adhesive 10kg and Laurel nitrogen
Ketone 0.4kg, the dissolving mixing is prepared into solution; Adopt curtain coating technology above-mentioned solution coat on backing layer, volatilize to solvent, protective layer on the cooling bonnet must " Gaowujiasu " picking.
Embodiment 8: " Gaowujiasu " picking
Lappaconitine: 0.11kg Mentholum: 1.8kg
Polyisobutylene PSA: 14kg;
Get lappaconitine 0.11kg, add Polyisobutylene PSA 14kg and Mentholum 1.8kg, the dissolving mixing is prepared into solution; Adopt curtain coating technology above-mentioned solution coat on backing layer, volatilize to solvent, protective layer on the cooling bonnet must " Gaowujiasu " picking.
Embodiment 9: " Gaowujiasu " picking
Lappaconitine: 1.8kg eucalyptus oil: 0.2kg
Polyisobutylene PSA: 5kg fatty acid Pyrusussuriensis is smooth: 21kg
Zinc oxide: 14kg;
Get lappaconitine 1.8kg, pulverizing adds Polyisobutylene PSA 5kg, eucalyptus oil 0.3kg, the smooth 21kg of fatty acid Pyrusussuriensis and zinc oxide 14kg, mixing and stirring again; Adopt curtain coating technology that said mixture is coated on the backing layer, volatilize to solvent, protective layer on the cooling bonnet, " Gaowujiasu " picking.
Claims (16)
1, a kind of Lappaconitine transdermal patch is formed by three layers, comprises backing layer, drug storehouse layer and protective layer, it is characterized in that the raw material of drug storehouse layer consists of:
Lappaconitine: 0.1-2 weight portion
Percutaneous absorption enhancer: 0.1-2 weight portion
Pressure sensitive adhesive: 5-15 weight portion.
2, Lappaconitine transdermal patch as claimed in claim 1 is formed by three layers, comprises backing layer, drug storehouse layer and protective layer, it is characterized in that the raw material of drug storehouse layer consists of:
Lappaconitine: 0.5 weight portion
Percutaneous absorption enhancer: 1 weight portion
Pressure sensitive adhesive: 10 weight portions.
3, Lappaconitine transdermal patch as claimed in claim 1 is formed by three layers, comprises backing layer, drug storehouse layer and protective layer, it is characterized in that the raw material of drug storehouse layer consists of:
Lappaconitine: 1 weight portion
Percutaneous absorption enhancer: 0.5 weight portion
Pressure sensitive adhesive: 12 weight portions.
4, Lappaconitine transdermal patch as claimed in claim 1 is formed by three layers, comprises backing layer, drug storehouse layer and protective layer, it is characterized in that the raw material of drug storehouse layer consists of:
Lappaconitine: 1.5 weight portions
Percutaneous absorption enhancer: 1.5 weight portions
Pressure sensitive adhesive: 8 weight portions.
5, as the arbitrary described Lappaconitine transdermal patch of claim 1-4, it is characterized in that also adding in the drug storehouse layer raw material cosolvent and/or plasticizer, the amount of cosolvent or plasticizer be the amount of the amount of lappaconitine, Percutaneous absorption enhancer and pressure sensitive adhesive amount total amount 1-5 doubly.
6, Lappaconitine transdermal patch as claimed in claim 5, it is characterized in that also adding in the drug storehouse layer raw material cosolvent and/or plasticizer, the amount of cosolvent or plasticizer is 3 times of total amount of the amount of the amount of the amount of lappaconitine, Percutaneous absorption enhancer and pressure sensitive adhesive.
7, as claim 1-4 or 6 arbitrary described Lappaconitine transdermal patch, it is characterized in that wherein Percutaneous absorption enhancer is meant Laurel nitrogen
In ketone, Mentholum, Borneolum Syntheticum, eucalyptus oil, Fructus Zanthoxyli oil, Oleum Bulbus Allii and Rhizoma Chuanxiong extract, Semen Myristicae extract, propylene glycol, methyl salicylate or the oleic acid one or more; Pressure sensitive adhesive is meant acrylate pressure sensitive adhesive, Polyisobutylene PSA, polysiloxanes pressure sensitive adhesive or thermo-elasto-plasticity rubber.
8, as the arbitrary described Lappaconitine transdermal patch of claim 5, it is characterized in that wherein Percutaneous absorption enhancer is meant Laurel nitrogen
In ketone, Mentholum, Borneolum Syntheticum, eucalyptus oil, Fructus Zanthoxyli oil, Oleum Bulbus Allii and Rhizoma Chuanxiong extract, Semen Myristicae extract, propylene glycol, methyl salicylate or the oleic acid one or more; Pressure sensitive adhesive is meant acrylate pressure sensitive adhesive, Polyisobutylene PSA, polysiloxanes pressure sensitive adhesive or thermo-elasto-plasticity rubber.
9, Lappaconitine transdermal patch as claimed in claim 5 is characterized in that wherein cosolvent is: the fatty acid Pyrusussuriensis is smooth, in polyoxyethylene aliphatic alcohol ether, Polysorbate, fatty glyceride or the polyoxyethylene fatty acid ester one or more are united use; Plasticizer is: one or more in Kaolin, zinc oxide, titanium dioxide, kieselguhr, glycerol or the propylene glycol are united use.
10, Lappaconitine transdermal patch as claimed in claim 6 is characterized in that wherein cosolvent is: the fatty acid Pyrusussuriensis is smooth, in polyoxyethylene aliphatic alcohol ether, Polysorbate, fatty glyceride or the polyoxyethylene fatty acid ester one or more are united use; Plasticizer is: one or more in Kaolin, zinc oxide, titanium dioxide, kieselguhr, glycerol or the propylene glycol are united use.
11, as claim 1-4 or 6 or the preparation method of the arbitrary described Lappaconitine transdermal patch of 8-10, it is characterized in that this method is:
Get the raw material mixing and stirring of drug storehouse layer; Adopt curtain coating technology that said mixture is coated on the backing layer to solvent and volatilize, protective layer on the cooling bonnet, Lappaconitine transdermal patch; Or said mixture is coated on the backing layer, protective layer on the cooling bonnet, Lappaconitine transdermal patch.
12, the preparation method of Lappaconitine transdermal patch as claimed in claim 5 is characterized in that this method is:
Get the raw material mixing and stirring of drug storehouse layer; Adopt curtain coating technology that said mixture is coated on the backing layer to solvent and volatilize, protective layer on the cooling bonnet, Lappaconitine transdermal patch; Or said mixture is coated on the backing layer, protective layer on the cooling bonnet, Lappaconitine transdermal patch.
13, the preparation method of Lappaconitine transdermal patch as claimed in claim 7 is characterized in that this method is:
Get the raw material mixing and stirring of drug storehouse layer; Adopt curtain coating technology that said mixture is coated on the backing layer to solvent and volatilize, protective layer on the cooling bonnet, Lappaconitine transdermal patch; Or said mixture is coated on the backing layer, protective layer on the cooling bonnet, Lappaconitine transdermal patch.
14, as claim 1-4 6 or the arbitrary described percutaneous plaster of 8-10 have application in the medicine of anti-inflammatory and analgesic effect in preparation.
15, percutaneous plaster as claimed in claim 5 has application in the medicine of anti-inflammatory and analgesic effect in preparation.
16, percutaneous plaster as claimed in claim 7 has application in the medicine of anti-inflammatory and analgesic effect in preparation.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNA2009101189289A CN101574331A (en) | 2009-01-08 | 2009-03-06 | Lappaconitine transdermal patch and preparation method thereof |
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN200910076270 | 2009-01-08 | ||
| CN200910076270.X | 2009-01-08 | ||
| CNA2009101189289A CN101574331A (en) | 2009-01-08 | 2009-03-06 | Lappaconitine transdermal patch and preparation method thereof |
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| Publication Number | Publication Date |
|---|---|
| CN101574331A true CN101574331A (en) | 2009-11-11 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNA2009101189289A Pending CN101574331A (en) | 2009-01-08 | 2009-03-06 | Lappaconitine transdermal patch and preparation method thereof |
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| Country | Link |
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| CN (1) | CN101574331A (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102178658A (en) * | 2011-05-03 | 2011-09-14 | 中国人民解放军第三军医大学第二附属医院 | Lappaconitine hydrobromide orally disintegrating tablets and preparation method thereof |
| CN108543076A (en) * | 2018-07-13 | 2018-09-18 | 邛崃市医疗中心医院 | Prevent the external medicine preparation of rheumatoid arthritis |
| CN112007592A (en) * | 2020-09-03 | 2020-12-01 | 中科芯云微电子科技有限公司 | Acid colloid for eliminating photoetching layout and protecting intellectual property of integrated circuit and application thereof |
-
2009
- 2009-03-06 CN CNA2009101189289A patent/CN101574331A/en active Pending
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102178658A (en) * | 2011-05-03 | 2011-09-14 | 中国人民解放军第三军医大学第二附属医院 | Lappaconitine hydrobromide orally disintegrating tablets and preparation method thereof |
| CN102178658B (en) * | 2011-05-03 | 2013-04-10 | 中国人民解放军第三军医大学第二附属医院 | Lappaconitine hydrobromide orally disintegrating tablets and preparation method thereof |
| CN108543076A (en) * | 2018-07-13 | 2018-09-18 | 邛崃市医疗中心医院 | Prevent the external medicine preparation of rheumatoid arthritis |
| CN112007592A (en) * | 2020-09-03 | 2020-12-01 | 中科芯云微电子科技有限公司 | Acid colloid for eliminating photoetching layout and protecting intellectual property of integrated circuit and application thereof |
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